Ongoing pulmonary capillary hemorrhage (PCH) induced by pulmonary diagnostic ultrasound (PDUS) in mammals is displayed as growing comet-tail artifacts in the image. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound in medicine. When discovered in 1990 using laboratory exposure systems, only harmless incidental diagnostic ultrasound exposure was expected, and no useful safety strategies arose from authoritative reviews in 2000 and 2008. However, direct PDUS now is becoming routine in formal and bedside clinical settings. Point-of-care ultrasonography often involves pulmonary examination by physicians not necessarily aware of PCH or the deficiency in safety. As bedside PDUS becomes routine worldwide, many patients will receive direct lung exposure and suffer a risk of PCH injury. Our objective is to fully understand PDUS-PCH and find solutions for this uniquely important safety issue. Novel and unexpected findings thus far have thoroughly revised our understanding of pulmonary injury by PDUS. PCH thresholds are virtually independent of ultrasound frequency and well below the Mechanical Index safety limit. Physiological factors, such as clinical sedatives, can be as important as physical exposure parameters. These worrisome findings overturn present PDUS safety assumptions and imply that sick people or patients taking certain medications may be most vulnerable to injury. Initial consideration of my hypothesis of acoustical radiation surface pressure for the physical mechanism of PCH only partly explained this bioeffect. Our central hypothesis is that PDUS-PCH arises from the interaction of ultrasound pulses with susceptible alveolar blood-air-barrier structures, generating capillary stress and failure. Our research has set the stage for rapid progress and three specific aims are planned using rigorous scientific method to ensure validity and reproducibility: First, the physiological susceptibility to PDUS- PCH will be determined for inhalation restriction, widely used medications, inflammation by pneumonia and sex. Second, the remaining physics of PDUS-PCH will be characterized, including the relative efficacy of imaging modes, the sites of initiation and progression of PCH in microscopical observations and the temporal evolution of PCH from nanoseconds to minutes. Finally, the propagation and interaction of ultrasound pulses within lung will be characterized by acoustical modeling at the scale of the acinus, by micro-scale finite element analysis of alveolar capillary architecture and blood-air-barrier stresses, and by research in swine, together with chest-wall dosimetry, for realistic translation of risk estimation to human patients. The outcomes expected from achieving these aims are an understanding of lung susceptibility in different patients, the elucidation of the physical mechanism causing PDUS-PCH, and a path to clinical safety assurance, with minimal loss of image quality, suitable for sonographer education and guidance. The overall impact of this project will be the initiation of new safety concepts for PDUS and the proactive solution of this emergent public health problem.